Inhibition of p53 transcriptional activity : A potential target for future development of therapeutic strategies for primary demyelination

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Jiadong Li
  • Cristina A. Ghiani
  • Aixiao Liu
  • Juan Sandoval
  • Jean DeVellis
  • Patrizia Casaccia-Bonnefil

Detail(s)

Original languageEnglish
Pages (from-to)6118-6127
Journal / PublicationJournal of Neuroscience
Volume28
Issue number24
Publication statusPublished - 11 Jun 2008
Externally publishedYes

Abstract

Oligodendrogliopathy, microglial infiltration, and lack of remyelination are detected in the brains of patients with multiple sclerosis and are accompanied by high levels of the transcription factor p53. In this study, we used the cuprizone model of demyelination, characterized by oligodendrogliopathy and microglial infiltration, to define the effect of p53 inhibition. Myelin preservation, decreased microglial recruitment, and gene expression were observed in mice lacking p53 or receiving systemic administration of the p53 inhibitor pifithrin-α, compared with untreated controls. Decreased levels of lypopolysaccharide-induced gene expression were also observed in vitro, in p53-/- primary microglial cultures or in pifithrin-α-treated microglial BV2 cells. An additional beneficial effect of lack or inhibition of p53 was observed in Sox2+ multipotential progenitors of the subventricular zone that responded with increased proliferation and oligodendrogliogenesis. Based on these results, we propose transient inhibition of p53 as a potential therapeutic target for demyelinating conditions primarily characterized by oligodendrogliopathy. Copyright©2008 Society for Neuroscience.

Research Area(s)

  • Demyelination, Microglia, Myelin, Myelin repair, Oligodendrocyte, Transcription

Citation Format(s)

Inhibition of p53 transcriptional activity : A potential target for future development of therapeutic strategies for primary demyelination. / Li, Jiadong; Ghiani, Cristina A.; Jin, Young Kim; Liu, Aixiao; Sandoval, Juan; DeVellis, Jean; Casaccia-Bonnefil, Patrizia.

In: Journal of Neuroscience, Vol. 28, No. 24, 11.06.2008, p. 6118-6127.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review